title: The waning of teriparatide effect on bone formation markers in postmenopausal osteoporosis is associated with increasing serum levels of DKK1.
abstract: BACKGROUND
  The effect of teriparatide (TPD) on bone turnover is initially exuberant but then diminishes. TPD is thought to stimulate bone formation by down-regulating the expression of specific Wnt antagonists, such as of sclerostin and Dickkopf-1 (DKK1).
  
  
  OBJECTIVE
  Our objective was to determine whether long-term treatment with TPD is associated with increasing serum levels of either sclerostin or DKK1.
  
  
  METHODS
  Ancillary observation was made of patients participating in a randomized clinical trial. PATIENTS, INTERVENTION, AND OUTCOMES: Fifty-five women with postmenopausal osteoporosis were randomly allocated to treatment for 18 months with either TPD 20 μg daily or placebo.
  
  
  RESULTS
  In the TPD group, both N-propeptide of type I collagen and C-terminal telopeptide of type I collagen rose significantly by 108 and 175% within the first 6 months. At month 18, the mean values decreased significantly compared with month 12 (-10 and -12%, respectively), but they were still significantly higher than baseline (+84 and 152%, respectively). Sclerostin remained stable over the entire study period in both groups. DKK1 did not change during the first 6 month of treatment, but only in the active group, it rose significantly at month 12 (median change +26.9%) and remained elevated at month 18 (+29.7%), at the time when the pharmacological effect of treatment with TPD appeared to be declining.
  
  
  CONCLUSIONS
  Long-term (>12 months) treatment with TPD is associated with an increase in serum levels of DKK1 that might be associated with the appearance of declining effect on bone formation markers.
authors.affiliation: University of Verona, Rheumatology Unit, Valeggio Hospital, via Ospedale, Valeggio 37067, Verona, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Gatti
authors.forename: Ombretta
authors.initials: O
authors.lastname: Viapiana
authors.forename: Luca
authors.initials: L
authors.lastname: Idolazzi
authors.forename: Elena
authors.initials: E
authors.lastname: Fracassi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Rossini
authors.forename: Silvano
authors.initials: S
authors.lastname: Adami
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins / Q000097:blood; D024042:Collagen Type I / Q000097:blood; D005260:Female; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects*; D015663:Osteoporosis, Postmenopausal / Q000378:metabolism*; D010455:Peptides / Q000097:blood; D011446:Prospective Studies; D019379:Teriparatide / Q000494:pharmacology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C422903:SOST protein, human; C052929:collagen type I trimeric cross-linked peptide; D019379:Teriparatide